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A functional sperm tail is essential for successful reproduction. Defects in its development often lead to infertility. This is also shown by a recent international study involving researchers from Würzburg.
The development of functional sperm is a highly complex process and a fundamental requirement for male fertility. Disruptions in this process are a common cause of infertility. However, the molecular mechanisms that control the precise structure of a sperm cell are still largely unknown. A particular challenge for research lies in the extremely small size of the cell structures involved, which are barely visible with conventional microscopes.
An international research team has now succeeded in using a specially developed method, ultrastructure expansion microscopy (U-ExM), to visualize the cellular architecture of germ cells in the highest optical detail, thereby elucidating the central role of a protein complex in the formation of the sperm tail.
The team applied this technique to specific substructures of male germ cells for the first time, enabling them to physically expand cellular components, like inflating a balloon, to make tiniest details of the cell accessible for analysis. The use of this cutting edge technology was key to deciphering the remodeling processes during sperm maturation and identifying a crucial molecular support structure.
Investigation at the Ultrastructural Level
The scientists published the results of their study in the journal Science Advances. Hiroki Shibuya and Yutaka Takeda from the RIKEN Center for Biosystems Dynamics Research in Kobe (Japan) were responsible for this work. Manfred Alsheimer, professor at the Chair of Cell and Developmental Biology (Zoology I) at Julius-Maximilians-Universität Würzburg (JMU), was also involved.
Alsheimer contributed his expertise in electron microscopy to help elucidate the structural role of a specific protein in sperm development. “My colleague from Japan asked me to investigate the function of this protein at the ultrastructural level using electron microscopy,” explains Alsheimer. Together with the data from high-resolution ultra-expansion microscopy collected by the colleague's group in Japan, the electron microscopic analyses performed at the Biozentrum provided new insights into the dynamic structure of centrioles and the role of the protein in sperm tail development.
A Molecular Scaffold as an Anchor for Motility
At the heart of these findings is a structure, the basal body, which serves a mechanical anchor for the sperm tail. The researchers discovered that during sperm maturation, a special internal scaffold made up of the proteins centrin and POC5 is massively reinforced in a tiny organizational center of the cell, known as the distal centriole. This centriole acts as the base to which the long, mobile flagellum – i.e., the sperm tail – is anchored.
What is special about this discovery is that this targeted reinforcement is a highly specialized adaptation that occurs exclusively in sperm. This process does not take place in other cells of the body that also form flagellum-like structures (cilia). The analysis also showed that the reinforcement is part of a complex maturation program that involves a complete realignment of the basal body’s architecture. This includes an unexpected change in geometry, in which the spatial arrangement of the two centrioles is reversed, as well as the targeted removal of proteins at the tip of the centrioles. But what would be the consequences if this crucial support structure were missing?
Without the Protein Scaffold: Male Infertility as a Direct Consequence
To demonstrate the exact function of the centrin-POC5 scaffold, the team studied mice in which the POC5 protein had been genetically removed. The results were clear:
• The male mice were physically completely healthy and showed no other developmental disorders.
• However, all males analyzed were 100 percent infertile.
• Detailed analysis showed that the absence of POC5 disrupted the structural integrity of the distal centriole, causing it to split pathologically into individual fibers and in some cases even fall apart completely. Without this stable anchor, no functional flagellum could form.
These results prove that the centrin-POC5 scaffold plays an indispensable role specifically in male reproduction, while, interestingly, it is not required for the formation of similar structures in other cell types. The study thus provides a fundamental new understanding of the molecular causes of certain forms of male infertility.
Building on these findings, the researchers now want to investigate which factors control this crucial remodeling process in sperm development. Although this is initially basic research, these insights could enable the development of new diagnostic approaches for infertility in the long term. The study thus deciphers a fundamental mechanism of sperm formation that is essential for successful reproduction.
Prof. Dr. Manfred Alsheimer, Chair of Cell and Developmental Biology (Zoology I), Phone: +49 931 31-84282, manfred.alsheimer@uni-wuerzburg.de
Centrin-POC5 inner scaffold provides distal centriole integrity for sperm flagellar Assembly. Yutaka Takeda, Eriko Kajikawa, Jingwen Wang, Morié Ishida, Manfred Alsheimer, Hiroki Shibuya. Science Advances, 3. Dezember 2025. DOI: 10.1126/sciadv.aea4045
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